RESUMEN

BACKGROUND: Tuberculosis (TB) is a leading cause of death in patients with human immunodeficiency virus (HIV)/AIDS. About 60% of HIV-positive individuals with latent TB infection (LTBI) develop active TB. Isoniazid preventive therapy (IPT) is recommended by the World Health Organization to prevent the progression of active TB in people living with HIV/AIDS (PLWHA). However, IPT implementation has been limited in some countries like Indonesia. The objective of this study was to assess the effect of IPT administration on the incidence of active TB in HIV patients with latent TB. METHODS: This was a quasi-experimental prospective cohort study conducted in an academic hospital in Indonesia. Interferon-gamma release assay-positive HIV-TB patients were randomly divided into an IPT group (received 6 months of IPT) and a non-IPT group. The incidence of active pulmonary TB was compared between the two groups after 6 months of follow-up. RESULTS: Of the 23 eligible patients, 22 were enrolled (10 in the IPT group, 12 in the non-IPT group). The incidence of active pulmonary TB was 0% in both groups. Factors associated with the absence of TB in both groups were the use of antiretroviral therapy for >4 years and a CD4+ T lymphocyte count >200 cells/µL. IPT was found to be safe with minimal adverse effects. CONCLUSIONS: In this setting, the use of long-term antiretroviral therapy and higher CD4+ counts, rather than just IPT, were the key factors associated with preventing active TB in latent HIV-TB patients. These findings suggest that comprehensive HIV management may be more important than IPT alone for TB control in PLWHA. Further research is needed to optimize TB prevention strategies in this high-risk population.

Asunto(s)

Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis Latente , Tuberculosis Pulmonar , Humanos , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Tuberculosis Latente/complicaciones , Masculino , Antituberculosos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Adulto , Femenino , Estudios Prospectivos , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Indonesia/epidemiología , Incidencia , Persona de Mediana Edad , Ensayos de Liberación de Interferón gamma

RESUMEN

BACKGROUND: At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. AIM: This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. MATERIALS AND METHODS: Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. RESULTS: 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%-99.2% of the subjects in Groups A-E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups (p < 0.05 and p < 0.0001) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups (p < 0.0001). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 (p < 0.0001) compared with day 1. Decreases in ALT and AST levels were observed in all groups (p < 0.0001). There was an increase in creatinine in the serum level of the Control, C, D, and E groups (p < 0.05), whereas the BUN level was elevated in all groups (p < 0.0001). CONCLUSIONS: The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.